4. The limbic system pathways

Allostatic load

Bruce McEwen at the Laboratory of Neuroendocrinology at Rockefeller University uses the terms allostasis and allostatic load to describe the effects of stress stimuli on the HPA axis and other neurobiological pathways. Allostasis is the physiological process by which bodily functions change to adapt to meet demands and challenges. It is a dynamic regulatory process to maintain balance or homeostatic control and cope during exposure to demands and changes (i.e. physical and behavioural stressors) when the allostatic load is moderate and short term. When the allostatic load is excessive or prolonged, it leads to wear and tear on biological systems, tissues and organs, resulting in chronic mental and physical disease.

Source: McEwen, B.S. (2008); McEwen, B.S. & Gianaros, P. (2010).

While the sensory systems bring in the information children need for development, the limbic system supplies the motivation for acting on the information. The limbic system is a complex set of structures that lies in the middle of the brain. It includes the hypothalamus, the amygdala and several nearby brain regions. The hypothalamus is one of the busiest parts of the brain and works like a thermostat. It is concerned with homeostasis, which is a process of returning body functions to some “set point.” The hypothalamus regulates hunger, thirst, response to pain, levels of pleasure, sexual satisfaction, anger and aggressive behaviour, and more. It also regulates the functioning of the autonomic nervous or arousal system and the hypothalamus-pituitary-adrenal (HPA) axis.

Two-year-old Avery is at the library with her grandfather. They are watching a puppet show together with a dozen other children. Avery is fascinated by the rabbit puppet that has just come onto the puppet stage and is asking all of the children to sing along. Avery joins in enthusiastically. From the left side of the puppet stage a growling sound is followed by a furry monster puppet who faces the audience and says in a menacing voice, “Yummy, yummy in my tummy. A tender rabbit for lunch.”

Avery sees that the rabbit is in danger and her face changes from enthusiasm to fear. She grasps her grandfather’s leg and climbs into his lap; her body has become tense. The rabbit turns to the furry monster and says, “Please come play with me. I have many friends today and we can all sing together.” Avery watches tentatively as the furry monster puppet slides over to the rabbit. As the rabbit holds out his paw in a welcoming gesture, the furry monster’s angry growls change to something closer to a cat’s purr. Now the rabbit is stroking the furry monster. Avery’s body relaxes and she looks up at grandpa, who is smiling. Avery’s smile returns, her body relaxes and she turns back to the stage and joins with others to sing the next song.

Two other children, the same age as Avery, have very different reactions as they watch the puppet show. Ashraf clutches his mother’s skirt as soon as the rabbit comes on stage. He watches intently but is not smiling and does not join the sing-along. When the furry monster appears on the stage, Ashraf ’s face crumbles and he begins to sob. His mother tries to comfort him, but he only sobs louder. She carries him out of the library and he is now thrashing about in the stroller as she walks toward home. Ashraf continues to sob uncontrollably until he falls asleep.

Jamel is also watching the puppet show. He sits quietly beside his older brother and does not join into the song. He gazes away from the puppets and stares out the window. He hears the furry monster puppet’s angry growl and glances back to the stage, but does not react. Instead, Jamel sits passively until the puppet show is over and his brother tells him it is time to go home.

Three children, the same age, living in the same neighbourhood, having the same experience—yet they respond quite differently. This process of arousal and recovery is drawing the keen attention of both scientists and educators. It is often termed self-regulation, which is perhaps a bad term because it is easily misused to mean behaviour management. Ashraf needs experiences that down-regulate his arousal state to be alert but calm. Jamel needs adults who are animated and engage his attention to upregulate his arousal state.

How we become engaged and excited and how we respond to new ideas, challenges, opportunities and frustrations is grounded in our biology. Often dubbed the “stress pathway,” this intricate neural network operates between the limbic system, adrenal glands, nervous system and prefrontal cortex parts of the brain to determine how we respond to stimuli. When we are aroused, our bodies release hormones that prime our readiness for action. We need to be aroused enough to become alert and engaged—an essential state for learning. If we sense a threat, our system is triggered to be on higher alert and our physiology responds—the classic fight or flight response introduced by Hans Seyle in the 1950s.19 Once the threat has passed or the challenge met, how and if we recover to a steady state—calmly focused and alert—depends on the flexibility of our limbic system.

Children begin life ready for relationships that drive early brain development.20, 21 An infant is primed to be interested in faces and initiate non-verbal communication with others. When we respond to an infant’s intense gaze, smiles or babbling we set up a chain of back and forth exchanges that are central to the wiring and sculpting of the limbic pathways. Primary caregivers mediate experiences that encourage the baby’s brain to become highly attuned to the quality of those early experiences. The ability of children to regulate their own emotions, behaviours and attention increases over time with maturation, experience and responsive relationships. The brain’s capacity for higher-level human functions, such as the ability to attend, interact with others, signal emotions and use symbols to think, build on the limbic system platform.

Studies in rats have been important in explaining how mammals respond to environmental stimuli. Rat pups that are poorly nurtured (a lack of licking and grooming) by their mothers at birth show an abnormal response to stress into adulthood. Michael Meaney, a psychobiologist at McGill University, showed that rat pups that are neglected in the first six days after birth have excessive methylation of the promoter region for the glucocorticoid receptor gene.22 Ordinarily, when the cortisol level is too high, this receptor can diminish cortisol production. The increased methylation changes the gene expression and the number of receptors expressed. Thus, stress produces high levels of cortisol in the blood, which can affect the brain and other organs in the body. The glucocorticoid receptors expressed in the hippocampus are sensitive to the glucocorticoid levels in the blood. If the receptor in the hippocampus is active, it will sense the increased cortisol levels in the blood and inhibit its production. If the receptor is not adequately functioning, the increased cortisol levels will persist.

Elevated levels of cortisol affect all tissues in the body and are a risk factor for disease. There is intense interest in how the HPA axis pathways and the prefrontal cortex can influence biological processes that contribute to the risk of mental and physical health problems in adult life. Cortisol stimulates the amygdala, which in turn activates the hypothalamus and shuts down the hippocampus. Stimuli to these pathways in the limbic system appear to affect brain development in the early years and is associated with depression in adulthood. They also appear to affect the biological pathways that affect arterial disease (atherosclerosis) and contribute to coronary artery thrombosis, heart attacks, carotid artery disease and strokes. These pathways, which are referred to as the limbic system, interact with the prefrontal cortex.31

Prenatal stress

“The history of man for the nine months preceding his birth would, probably, be far more interesting and contain events of greater moment than all the three score and ten years that follow it.”—Samuel Taylor Coleridge23

The study of fetal origins points to the nine months of gestation as a critical period for early human brain development and functioning of other major organs. The fetus grows in an environment heavily influenced by the surrounding air quality, chemicals and noise levels, as well as the mother’s health, nutrition, stimulation and even what languages it hears.24 For example, considerable evidence links maternal overeating during pregnancy to diabetes and other hormonal disorders in her offspring.25

In the United Kingdom, David Barker studied the physical health records of adults and correlated these data with early childhood records.26 His findings revealed that adversity, such as food scarcity during specific periods of fetal development, is related to a greater chance of coronary heart disease, stroke, type 2 diabetes and hypertension in later adult life. In one study, Barker showed that if the fetus showed abnormal growth, the risk of developing coronary heart disease as an adult increased.

The fetal origins of disease in later life seem to work through the impact of the in utero environment on the developing brain, particularly the early pathways related to the limbic system.

Researchers now believe that the pregnant mother’s stress level and emotional well-being are potent influences on how genes are expressed and on brain and biological development at birth and beyond. It appears that cortisol released by the mother’s HPA pathway crosses the placenta and transfers into the blood system of the fetus. When cortisol levels are consistently high, the developing neural circuitries that make up the limbic system are affected.27 The fetus responds to the cues it receives and builds its emerging limbic system pathways for a high stress environment with an easily aroused and slow to recover HPA pathway.28

Recent studies suggest that infants whose mothers experienced high levels of stress while pregnant, particularly in the first trimester, show signs of more irritability than other infants. Fetuses experiencing higher levels of stress also are slower to “habituate” as children. They find it difficult to tune out repeated stimuli—a skill that is linked to learning capacities.29

One study found that elevated cortisol during the early prenatal period was linked to lower cognitive abilities at age 1 year.30 But increased cognitive abilities were found among infants whose mothers had higher cortisol levels late in gestation, suggesting that timing matters.